Chromosome 22q11.2 Deletion Syndrome (22q11DS) is a common genetic microdeletion syndrome, with neurodevelopmental abnormalities in childhood. A remarkably high-risk of psychoses (25-40%) has been identified in adulthood/late adolescence. The relationship between the early neurodevelopmental abnormalities and psychoses in later life is unclear. The study of the neurodevelopmental and genetic abnormalities in children with 22q11DS would enhance the understanding of the trajectory that leads to schizophrenia in this vulnerable group as well as in the general population, since schizophrenia is thought to be a neurodevelopmental disorder. Our hypotheses are that the subset of 22q11DS children that is most vulnerable to psychosis would have: 1) pronounced and worsening abnormalities of neurocognition 2) pronounced and progressive morphological brain abnormalities of the frontal, temporal and parietal lobes, cerebellum and the corpus callosum 3) hemizygous genotypes within the 22q11.2 region that will be distinct from the rest with 22q11DS. These children would have an increased rate of prodromal symptoms and psychiatric disorders at the end of the study. We propose a longitudinal study of the neuropsychological and neuroanatomical changes, and genotype analysis of the hemizygous 22q11.2 interval in a cohort of 70 nonpsychotic children with 22q11 DS and 70 control participants. The aims are to: 1) Conduct a longitudinal assessment of neurocognition, including sustained attention, executive function and verbal working memory. We will also test for prodromal symptoms and psychiatric disorders. 2) Perform longitudinal brain morphometric analyses on magnetic resonance images (MRI) to quantify the corpus callosum, frontal, temporal, and parietal lobes and the cerebellum 3) Genotype specific single nucleotide polymorphisms (SNPs) in the genetic interval corresponding to the critical deleted area of the 22q11.2 region. An an exploratory aim, we will create haplotypes (linked genotypes) in the 22q11DS patients. These findings will be correlated with one another and will be predictive of the subset that will have elevated rates of prodromal symptoms and psychiatric diagnoses. Lay Summary: We will study the links between learning disabilities, brain structure and hereditary variants in the 22q11.2 region in children with 22q11 DS, a genetic condition with a high risk of schizophrenia, to understand the factors that play a role in this severe mental illness. [unreadable] [unreadable] [unreadable]